Automated diagnostic analyzer and method for its operation

ABSTRACT

An automated analyzer that receives samples prepared for analysis in an automated pre-analytical module and a method of operation of such automated analyzer. The automated analyzer includes a shuttle transfer station that receives a shuttle carrier from the automated pre-analytical system. The shuttle transfer station has a clamping assembly for the shuttle. The clamping assembly has jaws that advance engagement members into contact with a bottom portion of sample containers disposed in the shuttle. The clamping assembly secures the sample containers in the shuttle when sample is aspirated from the sample containers. The automated analyzer also has a multichannel puncture tool that is adapted to be carried by a robotic gripper mechanism. The multichannel puncture tool has multiple puncture members that each defines a channel Each channel is in communication with a different trough in the consumable. A pipette can pass through the channel in the puncture tool.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional application of U.S. application Ser.No. 16/088,939, filed on Sep. 27, 2018, allowed, which application is anational phase entry under 35 U.S.C. § 371 of International ApplicationNo. PCT/US2017/018298, filed Feb. 17, 2017, published in English, whichapplication claims the benefit of the filing date of U.S. ProvisionalApplication No. 62/326,395, filed Apr. 22, 2016, the disclosures ofwhich are hereby incorporated herein by reference.

BACKGROUND OF THE INVENTION

Diagnostic testing of biological samples is instrumental in the healthcare industry's efforts to quickly and effectively diagnose and treatdisease. Clinical laboratories that perform such diagnostic testingalready receive hundreds or thousands of samples on a daily basis withan ever increasing demand. The challenge of managing such largequantities of samples has been assisted by the automation of sampleanalysis. Automated sample analysis is typically performed by automatedanalyzers that are commonly self-contained systems which performmultistep processes on the biological samples to obtain diagnosticresults.

Several current automated clinical analyzers offer a user an array ofautomated tests or assays that can be performed on a provided sample.Additionally, when samples arrive at the laboratory, they are often notready for analysis. In order to prepare a sample for testing with anautomated analyzer, a lab technician typically transfers an aliquot ofthe sample from a primary container, as received by the laboratory, to asecondary container which is amenable to the analyzer. In addition, thetechnician typically must know what tests are to be performed on thesample so that the technician can select a test specific reagent ordiluent to be paired with the sample. This can be time consuming and canlead to operator error and exposure to communicable diseases.

Pre-analytical systems meant to help prepare a sample for analysis andfurther remove the operator from the workflow between the laboratory'sreceipt of a sample and the analyzer's test results also exist. However,many of these systems still require significant technician involvement,such as: prior to loading samples in the pre-analytical system; afterthe samples have been prepared by the pre-analytical system; and afterthe analyzers have completed analysis.

For example, some pre-analytical systems may automatically transfer analiquot of sample from a first container to a second container. However,such systems often require a technician to manually match identificationcodes of the first and second containers prior to loading them into thesystem, which can be time consuming and is prone to error.

In addition, many of these systems are not capable of being integratedwith one or more analyzers, and, conversely, the analyzers are notcapable of being integrated with such systems. In this regard, atechnician must be present to manually transfer the samples from thepre-analytical system to an analyzer and from the analyzer to a storagelocation once analysis is complete. This requires skilled labor toperform menial tasks and can create distractions in that the technicianmust be ever mindful of the progress of the samples within thepre-analytical system and analyzer so that the technician is prepared totransfer samples when ready in order to minimize downtime.

Moreover, current pre-analytical systems generally prepare samples atdifferent rates than the analyzers evaluate such samples. This furthercomplicates the integration between pre-analytical systems andanalyzers. In this regard, a technician may be required to continuouslykeep track of samples prepared by the pre-analytical system until a fullbatch of samples is accumulated for manual transfer to an analyzer.Alternatively, technicians may transfer partial batches to an analyzer,which can reduce the analyzer's productivity.

Thus, while current automated pre-analytical systems and analyzers arebeneficial to the clinical laboratory, there is room for betterintegration and automation of various systems.

BRIEF SUMMARY OF THE INVENTION

The present disclosure describes devices, systems, and methods forsample processing and analysis. In particular, an analyzer that isincluded in a high-throughput system is described. In one embodiment,the high-throughput system includes a pre-analytical system integratedwith the analyzer. In another embodiment, the high-throughput systemincludes at least an additional analyzer and a pre-analytical systemintegrated with both analyzers. These components (i.e., analyzers andpre-analytical system) are modular and are capable of being integratedin several different configurations to conform to a particularlaboratory's diagnostic needs.

The particular analyzer described herein generally has multiple decks orlevels in a vertical arrangement. One deck may house electroniccomponents and consumable waste which includes liquid waste and solidwaste. Another deck is a processing deck in which sample processing andanalysis take place. This deck also stores or inventories largequantities of consumables, which include pipette tips, reagent troughs,amplification plates, extraction container holders, a roll of plate sealmaterial and the like. In one embodiment, enough consumables can bestored on the analyzer to allow the analyzer to operate for an entire 8hour work shift at maximum throughput without reloading the system. Thisdeck may also include a plate sealer, orbital shakers, reagent troughpuncture tools, and readers/detectors for detecting an analyte, such asa DNA target.

A further deck includes a multipurpose robot which includes a Cartesianmovement system that allows a payload suspended from such system totraverse the interior of the analyzer above the processing deck. Thepayload includes a vision system, a consumable gripper, and amultichannel pipettor. The vision system providesbarcoding/identification abilities and to perform other machine visiontasks particularly as they relate to functions involving the gripper.The consumable gripper moves consumables about analyzer such as thereagent trough puncture tool and amplification plates. The multichannelpipettor performs all of the liquid handling requirements of theanalyzer.

BRIEF DESCRIPTION OF THE DRAWINGS

The features, aspects, and advantages of the present invention willbecome better understood with regard to the following description,appended claims, and accompanying drawings in which:

FIG. 1 is a front perspective view of a high-throughput diagnosticsystem according to one embodiment of the present disclosure.

FIG. 2 is a front perspective view of the second analyzer of the systemof FIG. 1 according to one embodiment of the present disclosure andabsent its external housing.

FIG. 3 is another front perspective view of the second analyzer of FIG.2 .

FIG. 4A is a perspective view of an extraction container holderaccording to an embodiment of the disclosure.

FIG. 4B is an exploded view of the extraction container holder of FIG.4A.

FIG. 5 is a perspective view of a sample container shuttle according toan embodiment of the disclosure.

FIG. 6 is a perspective view of an amplification plate according to anembodiment of the disclosure.

FIG. 7 is a perspective view of a liquid reagent trough assemblyaccording to an embodiment of the disclosure.

FIG. 8A is a top view of a processing deck according to an embodiment ofthe present disclosure.

FIG. 8B is a top perspective view of the processing deck of FIG. 8A.

FIG. 9A is a sample container retention assembly according to anembodiment of the disclosure.

FIG. 9B is a schematic view of the sample container retention assemblyof FIG. 9A engaging a sample container.

FIG. 9C is a partial perspective view of the sample container retentionassembly of FIG. 9A including a drip shroud.

FIG. 10A is a perspective view of a robot assembly according to anembodiment of the disclosure.

FIG. 10B is a side view of a payload of the robot assembly according toan embodiment of the disclosure.

FIG. 10C is a partial front perspective view of the payload of FIG. 10B.

FIG. 10D is a rear perspective view of a gripper of the payload of FIG.10B gripping an amplification plate.

FIG. 10E is a perspective view of a gripper according to anotherembodiment of the present disclosure.

FIG. 10F is a front perspective view of a multichannel pipettor of thepayload of FIG. 10B.

FIG. 11A is a front perspective view of a nest housing a puncture toolaccording to an embodiment of the disclosure.

FIG. 11B is a front perspective view of the puncture tool of FIG. 11A.

FIG. 11C is a schematic view of the puncture tool of FIG. 11A being usedto puncture a seal of a liquid reagent trough assembly.

FIG. 11D is a schematic view of the puncture tool of FIG. 11A inrelation to a pipette tip and the liquid reagent trough assembly of FIG.7 .

FIGS. 11E-11G depict an alternative puncture tool carrier and a methodof moving the puncture tool of FIG. 11A to and from the puncture toolcarrier using the robot assembly of FIG. 10A.

FIG. 12 is a rear, side perspective view of a consumable draweraccording to an embodiment of the disclosure.

FIG. 13A is a rear perspective view of a plate sealer according to anembodiment of the disclosure.

FIG. 13B is a rear perspective view of the plate sealer of FIG. 13Aincluding a lifting and pivoting mechanism.

FIG. 14 is a front perspective view of an orbital shaker according to anembodiment of the disclosure.

FIG. 15 is a block diagram of an exemplary architecture of a computingsystem involving the analyzer of FIG. 2 including example componentssuitable for implementing methodologies of the present disclosure.

FIG. 16 is a flow diagram of a method of using the analyzer of FIG. 2according to one embodiment of the present disclosure.

DETAILED DESCRIPTION Definitions

As used herein, the terms “about,” “generally,” and “substantially” areintended to mean that slight deviations from absolute are includedwithin the scope of the term so modified. Also when referring tospecific directions, such as left, right, front, back, up and down, inthe following discussion, it should be understood that such directionsare described with regard to the perspective of a user facing the belowdescribed system during exemplary operation.

HT System Generally

FIG. 1 depicts a high-throughput system 00 which includes a firstanalyzer 2000, a second analyzer 4000 and a pre-analytical system 10,such as the pre-analytical system described in U.S. ProvisionalApplication 62/296,349 (“the '349 Application”), the disclosure of whichis hereby incorporated by reference herein in its entirety. Theanalyzers 2000, 4000 and pre-analytical system 10 are modular such thatthey can be physically connected and disconnected from one another andalso electronically connected and disconnected from one another.Although second analyzer 4000 is different from first analyzer 2000 interms of the operations and assays they perform, it should be understoodthat first analyzer 2000 can be a duplicate of second analyzer 4000 sothat pre-analytical system 10 couples to at least two of the sameanalyzers. It should also be understood that the modularity ofpre-analytical system 10 allows it to couple to any analyzer soconfigured. As shown, first and second analyzers 2000, 4000 are disposedat opposite sides of pre-analytical system 10 in a linear arrangement.Although, pre-analytical system 10 and analyzers 2000, 4000 areconfigured for this physical arrangement it is contemplated thatpre-analytical system 10 can be configured to accommodate more than twoanalyzers and that pre-analytical system 10 and analyzers 2000, 4000 canbe configured so that they can be placed in other physical arrangementssuch as in an L-shape, for example.

Analyzer in Relation to System 10 & Viper LT

Second analyzer 4000 can be coupled to either side of pre-analyticalsystem 10. In this regard, a sample container shuttle transport assembly300 b of pre-analytical system 10, as shown of FIG. 7 of the '349Application, can extend toward analyzer 4000 when analyzer 4000 islocated to the left of system 10 (exemplified in FIG. 1 ), or a samplecontainer shuttle transport assembly 300 a of pre-analytical system 10can extend toward analyzer 4000 where analyzer 4000 is located to theright of system 10. Such assemblies 300 a-b may terminate adjacent tothe analyzer's threshold. However, as is described below, analyzer 4000is has a conveyor that can continue the path of a respective shuttletransport assembly 300 into analyzer 4000. As used herein, “shuttle” canbe an rack or carrier structure with a plurality of receptacles, eachreceptacle sized and configured to receive a sample container.

Analyzer 4000 is similar to and shares many characteristics with the BDViper™ LT System (Becton Dickinson, Franklin Lakes, N.J.) some of whichare identified below. The BD Viper™ LT System is not described in detailherein. However, as explained above, analyzer 4000 is a modular systemthat is configured to operate in cooperation with an automated systemfor pre-analytical processing of sample to be assayed using the BDViper™ LT System system. Such a pre-analytical system is illustrated assystem 10. In this regard, analyzer 4000 is an adaptation of the BDViper™ LT System for modular connectivity and high-throughput processingand analysis and, therefore, includes many additional features that arealso described below.

Structural Frame

As shown in FIGS. 2 and 3 , analyzer 4000 includes a structural framecomprised of several support components 4011, such as segments of metaltubing, which are configured to support and define various decks orlevels for sample processing and analysis. Such decks may include asupplementary deck 4012, a processing deck 4014, and a multipurposerobot deck 4016. Analyzer 4000 also includes a housing or shell 4010that surrounds its internal components, as shown in FIG. 1 .

Consumables

Intro

FIGS. 4-7 depict various consumables that can be automatically utilizedfor performing assays on samples, such as liquid based cytologicalsamples and the like. In particular, analyzer and its consumables areconfigured to perform HPV assays that detect for multiple stereotypes ofHPV (e.g., HPV 16, HPV 18, HPV 33, HPV 45, HPV 58, etc.). Such HPVassays may include, for example, the BD Onclarity™ HPV Assay (BectonDickinson, Franklin Lakes, N.J.). The ability to perform such assays ispartially supported by the consumable design. Such consumables includepipette tips 4062, sample containers 03, sample container shuttles 4030,extraction container holders 4020, amplification plates 4040, and liquidreagent trough assembly 4050.

Extraction Container Holder

Extraction container holder 4020 (FIGS. 4A and 4B) is preferably aplastic thermoformed clamshell that includes a lower portion 4025, upperportion 4022, and a plurality of extraction containers 4026. Eachextraction container 4026 may contain Ferric Oxide (“FOX”) particlesdisposed on a strip to extract DNA from samples and is sealed with alightweight foil 4023 that is penetrable with a pipette tip prior to theaddition of a sample.

The lower portion 4025 of the clamshell is a shallow, rectangular vesselwith through-holes extending therethrough to allow extraction containersto partially extend through such holes. Thermoformed features 4028 onsidewalls 4027 of the lower clamshell 4025 provide an interference fitwith features on a consumable drawer of analyzer 4000. Each ofextraction containers 4026 is loaded into lower portion 4025 so thattheir foil side faces the same direction as sidewalls 4027.

Upper portion 4022 of the clamshell is in the form of a ribbed insertthat drops into a space formed by sidewalls 4027 of lower portion 4025and locks via a set of protrusions (not shown) in the lower portion4025. A plurality of ribs 4024 extend in a direction transverse toextraction containers 4026 to provide structural stiffness to extractioncontainer holder 4020 which provides a holding force that helps retainupper clamshell 4022 during aspiration via a pipette. A plurality ofthrough-holes 4021 extend through upper portion 4022 between adjacentribs 4024 so as to allow foil seals 4023 of tubes 4026 to be accessed bya pipette tip. A barcode is located on upper portion 4022 which helpstrack information such as lot, expiration date, and serial number of thecontents of tubes 4026. Extraction container holder 4025 is assembledwith enough extraction containers 4026 to perform a single run which, inthe embodiment depicted, is 32 extraction containers in a 4×8arrangement.

Sample Container Shuttle

Sample container shuttle 4030 (FIG. 5 ) is similar to shuttle 284 of the'349 Application and includes receptacles 4032 each configured toreceive a sample container 03. The particular shuttle 4030 depictedincludes two rows of six receptacles 4032 for a total of twelvereceptacles. However, any number of receptacles 4032 can be provided.For example, shuttle 4030 may include two rows of twelve receptacles4032 for a total number of 24 receptacles. In the particular analyzer4000 depicted, a batch of samples may include 12-32. Thus, 1 to 3shuttles may provide a full batch to analyzer 4000.

Shuttle 4030 also includes transverse openings 4036 which intersect withcorresponding receptacles 4032 to allow a sample container retentionassembly (described below) to access containers 03 disposed therein.Sample containers 03 are the same as the third-type container 03 of the'349 Application. In this regard, sample containers 03 include caps witha penetrable seal 09.

Amplification Plate

Amplification plate assembly 4040 (FIG. 6 ) includes a plate body 4051.Engagement openings 4044 extend into respective sides 4042 of body 4041which allows a gripper of a multipurpose robot 4300 (FIG. 10A) to engageamplification plate assembly 4040 from opposing sides thereof. Forexample, openings 4044 a extend through side 4042 a and a side (notshown) directly opposite that of side 4042 a. In addition, openings 4044b extend through side 4042 b and through a side (not shown) directlyopposite that of side 4044 b. This allows robot 4300 to grip and liftplate 4040 while plate is in different orientations. A plurality oftubes that define amplification compartments 4045 are connected to platebody 4041 within openings thereof. Such tubes may be provided in theform of 1×8 strips of polypropylene tubes inserted into plate body 4051.Compartments 4054 are provided with dried down reagents that areutilized for amplification of a DNA target. In this regard,amplification plate 4040 may have color coding for visual identificationof the reagents contained in compartments 4045 of the plate 4040.However, in some embodiments, color coding may be absent.

Liquid Reagent Plate

Liquid reagent trough assembly 4050 includes about four separate andlinearly arranged troughs 4052 that house bulk reagents. For example,four troughs 4052 a-d may be provided so that a first trough 4052 acontains a wash buffer, a second through 4052 b contains an acid buffer,a third trough 4052 c contains a neutralization buffer, and a fourthtrough 4052 d contains an elution buffer. The volume of such troughs4052 is such that they can each contain sufficient reagent to perform atleast 20 assay runs. This allows sufficient volumes of reagent to beloaded onto analyzer 4000 to last an entire 24 hour period withouthaving to be restocked. First trough 4052 a includes tracks 4056integrated into its sidewall that allow baffling walls (not shown) to beinserted between such tracks 4056 and into trough 4052 a to help reducesplashing during the filling process. Second trough 4052 b generally hasthe smallest volume and defines a trapezoidal shaped cavity. This shapeprovides the requisite volume while also providing a relatively largeopening area at one side of the cavity to enable piercing with asufficiently large tool, such as tool 4240, through which a pipette tipaccesses trough 4052 b

Assembly includes a heavy duty, penetrable lidding material 4058 (seeFIG. 11C) that can be penetrated by puncture tool 4240 (see FIG. 11B) toallow a pipette tip 4062 to access the reagents, as is described below.Liquid reagent trough assembly 4050 also includes a collar 4054extending around a perimeter thereof that rests on a deck surface andthat may be engaged by toggles on the deck surface to hold down assembly4050.

Pipette Tips

Pipette tips 4062 are provided in tip holders 4060 (See FIG. 8B). In oneembodiment of analyzer four 1000-μL tips are used to process eachsample. In addition, a single reagent pipette tip is used with eachbatch of samples. This helps reduce the number of tips utilized as thereagent pipette tip does not come into direct contact with samples.

Referring back to FIGS. 2 and 3 , supplementary deck 4012 is disposedadjacent the bottom of analyzer 4000 and is located beneath processingdeck 4014. Supplementary deck 4012 houses electronic components andwaste repositories. For example, supplementary deck 4012 can include aliquid waste repository 4002 that receives and houses all liquid waste,such as from extraction tubes 4026 during a DNA extraction process andfrom liquid reagent trough assembly 4050 during an emptying process.This repository 4002 includes a sensing apparatus to monitor emptycapacity. Supplementary deck 4012 also includes one or more solid wasterepositories 4004 that sit below each of solid waste chutes 4210 (seeFIGS. 8A and 8B) that extend through processing deck 4014. For example,a single waste repository may be located under waste chutes 4210 and maycollect all solid waste. In another example, two solid wasterepositories may be used to collect used pipette tips 4062 andamplification plates 4040, respectively. Each of such aforementionedsolid waste repositories may contain a sensing apparatus similar toliquid waste repository 4002 for detecting solid waste level. Suchsensing apparatus can include an optical or ultrasonic sensor, forexample.

Processing Deck

Layout

FIGS. 8A and 8B depict the processing deck 4014. Processing deckincludes consumable drawers 4100, a plate sealer 4220, orbital shakers4230, piercing tools 4240, reagent trough assemblies 4050, a shuttletransfer station 4250, waste chutes 4210 and readers/detectors.

Drawers

In the embodiment depicted, processing deck 4014 includes six consumabledrawer assemblies 4120, each of which houses the majority of theconsumables utilized in an assay workflow, as shown in FIGS. 8A, 8B and12 . In this regard, each of the six drawers 4100 includes from front toback, a pipette tip station 4124, extraction container station 4126, andamplification plate station 4128. Stations 4124, 4126 and 4128 areconfigured to hold pipette tip holders 4060, extraction containerholders 4020, and amplification plates 4040, respectively. In addition,each consumable drawer 4120 houses an extractor module 4125 within itshousing 4122, which is similar to the extractor module of the BD Viper™LT System, and includes moveable magnets which provides the movablemagnetic field that is utilized to extract DNA from the samples. Suchmagnets are housed in each consumable drawer 4120 beneath extractorcontainer station 4126 and are selectively moveable in an up-downdirection along rails 4127 which are disposed on sidewalls separatingcompartments beneath each of stations 4124, 4126 and 4128. As depictedin FIG. 12 , extractor 4125 is in an up/extraction position. Consumabledrawer assemblies 4120 sit at the front of analyzer 4000 between twodetector/readers 4260 a-b and each include a visual indicator, such as acolored LED, on a front end thereof that indicates its status to a userto let a user know that the drawer is currently being used, is ready tobe used, or needs replenishing with consumables.

Drawer assemblies 4120 also include a hinged retention feature 4121. Inthe depicted embodiment, retention feature 4121 is a spring loaded armthat is hingedly connected to housing 4122 immediately behind extractioncontainer station 4126. Retention feature 4121 has a retention positionand consumable replacement position. In the retention position, as shownin FIG. 12 , retention feature 4121 extends over stations 4124 and 4126.In this position, retention feature 4121 is configured to encompassrespective perimeters of a pipette tip holder 4060 and an extractioncontainer holder 4020 that are located in their respective stations4124, 4126 while allowing access thereto via openings in retentionfeature 4121. In this regard, retention feature 4121 prohibits anextraction container holder 4020 and pipette tip holder 4060 from beinginadvertently moved during operation. When consumables in drawer 4120need to be replaced, drawer 4120 is extended and a locking feature (notshown) that locks retention feature 4121 in the retention position isreleased. Under the bias of a torsion spring (not shown) located withinhinge 4123, retention feature 4121 rotates about hinge 4123 to theconsumable replacement position which provides clearance for a user toreplenish consumables within drawer 4120.

Processing deck 4014 also includes a single tip drawer assembly 4110that houses five 96-well tip carriers 4060 and is similarly constructedto drawers 4120 in that it is includes visual indicators on a front endthereof. However, tip drawer assembly 4110 does not include an extractorand is configured to hold multiple tip carriers 4060. These tip carriers4060 provide both the fourth pipette tip utilized for each sampleextraction (conducted in the consumable drawers), along with reagenttips and any excess tips that may be needed due to pick-up failures orclogs. This drawer 4110 sits to the left of the consumable drawers 4120.These drawers 4110, 4120 can be accessed from the front of analyzer 4000by a user and may be automated in that they are automatically locked orunlocked by analyzer 4000 depending on their present status and thestatus of the analyzer as a whole.

Reagent Trough Station

Reagent trough assemblies 4050 are located in a reagent trough stationwhich is located between consumable drawers 4120 and orbital shakers4230. These assemblies 4050 remain in a fixed position. Although reagenttrough assemblies 4050 remain in a fixed position and are generally notaccessible during operation like consumable drawers 4100, it should beunderstood that reagent trough assemblies 4050 include sufficient enoughreagent that it should not be necessary to access this area duringoperation.

Waste Chute Separate waste chutes 4210 for amplification plates 4050,pipette tips 4062, and liquid waste extend through processing deck 4014and communicate with respective waste repositories 4002, 4004. Theseallow used consumables to be routed to waste repositories 4002, 4004located below the processing deck. Waste chutes 4210 sit behind tipdrawer 4110 toward the back of analyzer 4000.

Sealer

FIGS. 13A and 13B depict a fully-automated plate sealer 4220 which islocated at the rear left corner of the analyzer 4000. Plate sealer 4220has a moveable platform 4224 that receives an inoculated amplificationplate 4040 and moves into plate sealer 4220, best shown in FIG. 13A.Plate sealer 4220 bonds a clear, optical seal to the top ofamplification plates 4040. Analyzer 4000 uses automated plate sealer4220 to seal an amplification plate 4040 following elution and prior toplate mixing and target amplification. In order to provide multi-sealingcapability upon a single load, sealer 4220 utilizes a roll-based sealwhich can be provided by a single roll 4222 of seal material, such as an800 meter roll, that can be loaded at once. This volume of seal materialis sufficient to seal plates 4040 for a full year for most applications.However, plate sealer 4220 may include an optical sensor (not shown)that is configured to sense when the amount of seal material dropsbeneath a certain threshold level indicating that the seal materialshould be replaced.

Although plate sealer 4220 is located in the rear of analyzer 4000, itis desirable to be able to access sealer 4220 from the front of analyzer4000 for replenishment of seal material. The ability to accesscomponents in the rear of analyzer 4000 through the front of analyzer4000 allows analyzer 4000 to be placed directly against a wall in alaboratory, which helps conserve floor space. To facilitate frontalaccess, plate sealer 4220 may be mounted on a lifting and pivotingmechanism 4226, as best shown in FIG. 13B. The lifting and pivotingmechanism 4226 includes a moveable base 4227 (see FIG. 13A) mounted to adrive shaft (not shown). The drive shaft is surrounded by a rotatablesleeve 4229 which is also connected to moveable base 4227 and isrotatable therewith. When the optical sensor senses that seal materialis running low, a user is notified. The user may then manually orautomatically operate crank 4228 to raise moveable base 4227 via thedrive shaft until it clears the deck surrounding it. In this liftedposition, moveable base 4227 is manually or automatically rotatedcounter-clockwise to present the rear of sealer 4220 to the front ofanalyzer 4000. This rotation is limited by the presence of a rotationalstop arm 4223 which is connected to rotatable sleeve 4229 that surroundsthe drive shaft. In this regard, rotational stop arm rotates in unisonwith sleeve 4229 and base 4227 until stop arm abuts stationary structurethereby preventing further rotation. This helps prevent over-rotationwhich can result in incidental contact of plate sealer 4220 with otherequipment. In this position, the empty or near empty roll 4222 of sealmaterial can be easily reached from the front of analyzer 4000 forreplacement. Once a new roll 4222 is attached, sealer 4220 can berotated clockwise and crank 4228 operated to lower sealer 4220 back intoits operating position.

Puncture Tools

Puncture tool 4240 (see FIGS. 11A-11D) includes a plurality ofcannulated puncture members 4244 that extend from a tool body 4241 andhave a puncturing end 4246 shaped to puncture the heavy duty seal ofreagent trough assemblies 4050. Such cannulated puncture members 4244may or may not be co-located in a vertical plane parallel to alongitudinal axis of tool body 4241. Cannulated puncture members 4244define openings 4242 sufficiently large to receive a pipette tip 4062therein. Tool 4240 also includes a pair of linking members 4248extending upwardly from body 4241 that have engagement openings 4249that receive holding members 4346 of a gripper 4340 of robot 4300, asshown in FIG. 11C. Puncture tool 4240 punctures a seal of a reagenttrough assembly and is left in place to provide channels through whichpipette tip 4062 can aspirate liquid reagents, as best shown in FIG.11D.

Puncture Tool Nests/Carriers

Two puncture/piercing tools, each associated with a reagent troughassembly 4050, sit within respective nests or carriers 4270 toward thecenter rear of processing deck 4014 until they are used to puncture areagent trough assembly 4050. Carrier 4270 includes a platform 4272 thatis within a cavity 4274 that houses tool 4240. Platform 4272 has raisedside edges that are keyed to the periphery of tool 4240 so that whentool 4240 is placed in carrier 4270, tool 4240 rests on platform 4272 ina precise location as it waits to be picked up by robot 2300, as bestshown in FIG. 11A.

FIGS. 11E-11G illustrate depict an alternative puncture toolnest/carrier 4280. Carrier 4280 includes a base 4282, one or moresidewalls 4288, alignment posts 4287 a-b, and retaining members 4284.Posts 4287 a-b extend from base 4282 and have tapered end portions 4289that are configured to interface with openings (not shown) at a bottomof puncture tool body 4241. Tapered end portions 4289, which are bestshown in FIG. 11G, help align tool 4240 within carrier 4280 when placedthereon. The one or more sidewalls 4288 extend from base 4282 generallyat a front and back side of carrier 4280 which defines a housing spacefor tool 4240. As shown, sidewalls 4288 do not extend from base 4282 atleft and right sides thereof which provides space for retaining members4284 to pivot. However, sidewalls extending from a left and right sideof base 4282 to further define the housing for puncture tool 4240 arecontemplated provided such sidewalls supply enough clearance formovement of retaining members 4284, as described below.

Retaining members 4284 extend from base 4282 and are located at oppositeends of carrier 4280 a distance sufficient to allow puncture tool 4240to be disposed therebetween. Retaining members 4284 each include one ormore beveled surfaces 4285, such as first and second beveled surfaces4285 a-b. Beveled surfaces 4285 a-b face inboard toward a center ofcarrier 4280. In addition, the second beveled surface 4285 b isgenerally positioned more inboard than the first beveled surface 4285 a.Each retaining member 4284 also has an overhanging surface 4286 thatfaces base 4282. Retaining members 4284 are movable between first andsecond positions, such as by a pinned connection to the base 4280, butare biased in the first position, such as by a spring (not shown). Inthis regard, when retaining members 4284 are in the first position, apuncture tool 4240 supported by carrier 4280 is constrained fromvertical movement by overhanging surfaces 4286 of retaining members4284, as depicted in FIG. 11E. While in the second position, as shown inFIG. 11F, overhanging surfaces 4286 are disengaged from puncture tool4240. Thus, puncture tool 4240 is no longer constrained by retainingmembers 4284 and can be lifted from carrier 4280 while retaining members4284 are in the second position.

Sample Container Retention Assembly

Sample container retention assembly 4250 (FIGS. 9A and 9B) is similar tosample container retention assembly 1100 of the '349 Application in thatit includes a clamping assembly 4252 that closes toward a shuttle 4030disposed within the clamping assembly to retain shuttle 4030 andcontainers 03 within the shuttle 4030 while aliquots are aspirated fromcontainers 03. In this regard, clamping assembly 4252 includesengagement members 4253 which are configured to project through secondtransverse openings 4036 in shuttle 4030 when clamping assembly 4250 isclosed to engage a skirt 07 at a bottom end of sample containers 03, asbest seen in FIG. 11C. These engagement members 4253 penetrate/bite intoskirts 07 of respective containers 03 to prevent containers 03 frombeing inadvertently removed from shuttle 4030 during aspiration. Inaddition, each clamping assembly 4252 includes a drip shield 4251connected thereto. Each drip shield 4251 includes a plurality ofsemicircular notches that are configured to partially receive a samplecontainer 03. In this regard, when clamping assemblies 4252 engagesample containers 03, as shown in FIG. 9A, the drip shields 4251 of therespective clamping assemblies 4252 interface so as to substantiallyfill the gaps between sample containers 03 which helps prevent sampledrippage from falling between containers 03 and onto shuttle 4030 orconveyor 4254. To provide further drip protection, a drip shroud 4259may cover clamping assembly 4250 except directly above sample containers03 and conveyor 4254, as best shown in FIG. 9C. Drip shields 4251 anddrip shroud 4259 provide easy-to-clean surfaces in the event of sampledrippage.

In addition, sample container retention assembly 4250 includes aconveyor belt 4254 that receives a shuttle from pre-analytical system 10and moves it into position between clamping assembly 4252. In thisregard, conveyor belt 4254 receives a shuttle 4030 from an output laneof the shuttle transport assembly 300 of pre-analytical system 10. Whenit is time to return shuttle 4030 to pre-analytical system 10, a motor4256 operates a drive mechanism (not shown) that slides retentionassembly 4250 along a track 4257 on a suspended platform 4255 so thatconveyor 4254 aligns with an output lane of the shuttle transportassembly 300. Conveyor 4254 operates in two directions so as to receiveand return shuttle 4030.

Orbital Shaker

Orbital shakers 4230 (see FIG. 14 ) oscillate sealed amplificationplates 4040 in a circular motion to fully rehydrate a dried down reagentmixed with an eluted sample within the compartments 4045 of the sealedamplification plate 4040. Two of these are positioned at the center rearof analyzer 4000 behind extraction reagent troughs 4050. Of course moreor less could be provided as needed. Orbital shaker 4040 includes aplatform 4042 upon which amplification plate 4040 rests and includes atleast two automated arms 4046 that are configured to hold plate 4040 onplatform 4042 during operation. In this regard, arms 4046 may bepositioned at corners of platform 4042 and may move inwardly in a radialdirection to hold amplification plate 4040 in position and outwardly ina radial direction to release amplification plate 4040 for pick up byrobot 4300.

Detector/Reader

Two detector/readers 4260 a-b are located at opposite ends of analyzer4000 and have cavities that face the center of analyzer 4000. Thesereaders 4260 a-b are similar to the readers utilized in the Viper™ LTSystem. In this regard, readers 4260 a-b have a housing that receivessealed amplification plates 4040. Readers 4260 a-b also have athermocycler that are used to amplify a target analyte withinamplification plates 4040, and a detector that detects the targetanalyte using a set of LED illuminators, for example

Robot

As depicted in FIGS. 10A-10F, multipurpose robot 4300 is suspended atthe robot deck 4016. Multipurpose robot 4300 is an automated system formass transfer and optical interrogation (e.g., barcode reading) thathangs above processing deck 1014 and includes a Cartesian robot 4301which carries a payload.

Cartesian robot 4301 includes two linear rails 4302 a-b mountedorthogonally. Each of the two linear rails 4302 a-b has at least twooptical limit sensors (not shown) to ensure the payload 4306 is notdriven to their extent and to facilitate initialization. Because of thesize of payload 4306 and the fact that it hangs near processing deck4014, there are potential collisions that are desirably avoided. To helpprevent collisions, a third optical sensor on first linear rail 4302 ais provided. This allows robot 4300 to instantaneously sense which halfof the analyzer (left/right) it is located, ensuring that the center ofanalyzer 4000 can be found and a safe start-up and initializationprocedure can be used.

Payload and Rotational Stage

Robot payload 4306 sits beneath Cartesian robot 4301 and providesvision, pipetting and plate transfer functionality. In this regard,payload 4306 includes a rotational stage 4310, vision system 4320,gripper module 4340, multichannel pipettor 4350, and a backplaneconnector 4360. Robot payload 4306 is connected to Cartesian robot 4301via rotational stage 4310. Rotational stage 4310 can rotate payload 4306about 180 degrees about a vertical axis which provides movementflexibility to gripper 4340, pipettor 4350 and vision system 4320.

Consumable Handling Portion

Vision System

Vision system 4320 and gripper 4340 comprise a consumable handlingmodule 4320. Vision system 4320 can be any conventional vision systemthat is capable of reading barcodes and performing other machine visiontasks. An exemplary vision system includes the In-Sight 5600 visionsystem (Cognex Corporation, Natick, Mass.). This vision system 4320 isaffixed to the vertical stage 4322 along with gripper 4340 allowingvision system 4320 to be moved up and down along with gripper 4340 andallowing vision system 4320 to focus on a target. Such movement alongvertical stage is performed by motor 4330.

Gripper

Gripper module 4340 sits on an opposite side of backplane connector 4360from multichannel pipettor 4350. Gripper module 4340 includes, asmentioned, is connected to vertical translation stage 4322 that variesthe height of the gripper 4340 and arms 4344 a-b that translatehorizontally relative to each other to engage a consumable item. Sucharms 4344 have gripper fingers 4349 (see FIG. 11C) that may haveengagement features or protrusions 4345 that project sideways therefromand that are used to help secure a consumable item that hascorresponding engagement notches (see FIG. 11C). Gripper 4340 alsoincludes holding members 4346 that project downwardly from horizontalmembers 4347 of each arm 4344 a-b (see FIG. 11C). Such holding members4346 each include a sideways projecting member 4348 that is configuredto be received by an engagement opening 4249 in linking members 4248 ofpuncture tool 4240. As each arm 4344 is capable of moving relative toeach other, each holding member 4346 is capable of moving relative tothe other holding member. This allows holding members 4346 to engagelinking members 4248 so as to firmly secure puncture tool 4240 during apuncture operation, and to also disengage puncture tool 4240 so as leaveit in place within carrier 4270, 4280 or atop liquid reagent troughassembly 4050. Similar to the movement of the gripper arms describedelsewhere herein, the holding members are capable of relative lateralmovement such that they are laterally farther apart in one position andlaterally closer together in another position.

FIG. 10E depicts an alternative gripper module 4340′. Gripper module4340′ is similar to gripper module 4340 in that it includes gripper arms4344 a′-b′ which include protrusions 4345. However, gripper module 4340also includes presence sensors 4341 that are configured to detect thepresence of a consumable item between gripper arms 4344 a′-b′. Forexample, as shown, each arm 4344 a′ and 4344 b′ includes a sensor 4341that is a switch-type sensor. Such sensor 4341 is positioned so that itcan be deflected by a consumable item, such as plate 4040, as gripperarms 4344 a′-b′ grip such consumable item therebetween. Thus, as long asgripper arms 4344 a′-b′ grip the consumable item so that a sensor 4341is deflected, its presence is detected. However, when gripper arms 4344a′-b′ release their grip, sensor 4341 returns to its normal positionindicating that no consumable item is present. Although a deflectable,switch-type sensor is shown. Other sensors are contemplated, such asoptical sensors, for example.

A method of puncturing liquid reagent trough assembly 4050 is depictedin FIGS. 11E-11G and also 11C-11D. As shown in FIG. 11E, puncture toolcarrier 4280 Is mounted to processing deck 4014 and puncture tool 4240is retained in carrier 4280 by retaining members 4284 which are in thefirst position. Such a carrier 4280 may be located in the back rightcorner of system 4000 adjacent to the orbital shakers 4230 shown in FIG.8B. Multipurpose robot 4300 moves to the puncture tool carrier 4280 andlowers the gripper module 4340 to a height above puncture tool 4240 sothat projecting members 4348 of gripper are aligned with engagementopenings 4249 (see FIG. 11B for openings) of puncture tool 4240, whichis best shown in FIG. 11E.

While in this position, gripper arms 4344 a-b are moved apart so thatprojecting members 4348 are received in corresponding engagementopenings 4249. As this occurs, gripper fingers 4349 engage retainingmembers 4284 at first beveled surface 4285 a, or adjacent thereto, so asto overcome their bias and push the retaining members 4284 outwardlytoward the second position, as best shown in FIG. 11F. This providesclearance for puncture tool 4240 to be lifted from contact with carrier4280. Thus, with the retaining members 4284 being held in the secondposition by fingers 4349 and with projections 4348 engaging openings4249, puncture tool 4240 is removed from carrier 4280 via gripper module4340 until puncture tool body 4241 clears overhanging surface 4286 ofretaining members 4284.

Once puncture tool 4280 clears retaining members 4284, multipurposerobot 4300 moves gripper module 4340 and puncture tool 4280 toward aliquid reagent trough assembly 4050 which may be positioned in front oftool carrier 4280 and more toward the center of system 4000, as shown inFIG. 8B. Robot 4300 then positions puncture tool 4280 over troughassembly 4050 so that cannulated puncture members 4244 are each alignedwith a respective trough 4052 a-d, as best shown in FIG. 11C.Thereafter, gripper module 4340 lowers puncture tool 4240 so thatpuncture members 4244 puncture lidding material 4058. When liddingmaterial 4058 is fully punctured, tool body 4241 sits on the walls 4051that separate each trough 4052 a-d. Such walls 4051 support the weightof puncture tool 4240. Cannulated puncture members 4244 have a lengthsufficiently long to penetrate entirely through lidding material whilebeing sufficiently short to position puncture members 4244 entirelyabove the surface of whatever reagent is located in the respectivetroughs 4052 a-d. In addition, cannulated puncture members 4244 provideuniform openings 4242 that are sufficiently large to allow easy passageof a pipette tip 4062. This helps prevent incidental contact with thelidding material 4058 that could jostle a quantity of reagent free ofpipette tip 4062 as pipette tip 4062 is used to draw reagent from troughassembly 4050.

Once lidding material 4058 is punctured and tool 4240 is well supportedby trough assembly 4050, gripper module 4340 releases its grip on tool4240 by moving arms 4344 a-b toward each other so that projections 4348are removed from openings 4249. Thereafter, the robot 4300 carriespayload 4310, which includes gripper module 4340, away from troughassembly 4050. In this regard, payload 4310, which also includespipettor 4350, may move to a location of unused, disposable pipette tips4062 which may be located in the tip drawer 4110 shown in FIG. 8B.Thereafter, pipettor 4350 is lowered so as to retrieve one or morepipette tips 4062. Robot 4300 may then move pipettor 4350 over puncturetool 4240 and trough assembly 4050 so as to align pipette tip 4062 withan opening 4242 of tool 4240. The pipette tip 4062 is then lowered intothe selected trough 4052, as shown in FIG. 11D, through thecorresponding opening 4242 so as to aspirate reagent from the trough4052. The aspirated reagent may then be carried to another locationwithin system 4000 as needed. The reagent is then dispensed into anappropriate container and the pipette tip 4062 is disposed of. Theretrieval of a pipette tip 4062, aspiration of a reagent throughpuncture tool, and disposal of the pipette tip 4062 may occur multipletimes over until the reagent is depleted. System 4000 keeps track of theamount of reagent remaining and will alert a user when such reagentneeds to be changed. This is described elsewhere herein.

When puncture tool 4240 is returned to carrier 4280, such as when liquidreagent trough 4050 needs to be replaced or for some other reason, robot4300 moves gripper module 4340 over puncture tool 4240 which is restingon reagent trough assembly 4050 and engages puncture tool 4240 by movingprojections 4348 into openings 4249, as previously described. Oncepuncture tool 4240 is engaged by gripper assembly 4340, robot 4300carries puncture tool 4240 away from reagent trough assembly 4050 to aposition above carrier 4280. Gripper assembly 4340 is then lowered sothat puncture tool body 4241 contacts one or more of beveled surfaces4285 a-b. As puncture tool 4240 is lowered toward carrier 4280, puncturetool body 4241 slides along one or more of beveled surfaces 4285 a-bwhich pushes retaining members 4284 outwardly from the first position tothe second position, as best shown in FIG. 11G. With retaining members4284 positioned to provide clearance for puncture tool 4240, puncturetool 4240 is further lowered so as to engage posts 4287 a-b which alignspuncture tool 4240 relative to carrier 4280. Near the bottom of thedescent of puncture tool 4240, gripper fingers 4349 may also engageretaining members 4284 at or adjacent to beveled surface 4285 a to helpkeep them in the second position, which is illustrated in FIG. 11F. Oncetool 4240 is fully seated on carrier 4280, gripper arms 4344 a-b aremoved laterally toward each other which disengages projecting members4348 from puncture tool 4240 and also disengages gripper fingers 4349from retaining members 4284. Said another way the pair of gripper armsmove laterally from a first position in which the arms are further apartto a second position in which they are closer together. The gripperfingers engage and push back on the retaining members in the fartherapart position and do not engage retaining members when in their closertogether position. In this regard, retaining members 4284 return to thefirst position shown in FIG. 11E under their own bias, thereby retainingpuncture tool 4240 until it is needed again.

Multi-Channel Pipettor

Multichannel pipettor 4350 is connected to backplane connector 4360 atan opposite side thereof than consumable handling portion. Multichannelpipettor 4350 includes a plurality of liquid handling assemblies 4352a-e that directly connect to backplane connector 4360. In the embodimentdepicted, there are five liquid handling assemblies 4352: a first liquidhandling assembly 4352 a, a second liquid handling assembly 4532 b,third liquid handling assembly 4532 c, a fourth liquid handling assembly4532 d, and a fifth liquid handling assembly 4532 e. Each liquidhandling assembly 4532 includes a main board assembly 4370 and a pipetteassembly 4380. Liquid handling assemblies 4352 a-e are connected tobackplane connector 4360 adjacent to one another in close proximity.

Each main board assembly 4370 a-e helps provide data, power andpositive/negative air pressure to a corresponding pipette assembly 4380a-e. In the embodiment depicted, there are five pipette assemblies 4370a-e. Each main board assembly 4370 a-e is similar to the main boardassembly 1401 described and shown in FIGS. 27A and 27B of the '349Application. In this regard, each main board assembly 4370 a-e includesa housing 4372 with various components disposed therein, such as a PCB,positive and negative pressure inputs, a valve, and a liquid/gas conduitin communication with the inputs and valve. Main board assemblies 4370a-e also includes a z-drive mechanism that includes a vertical rail 4374on one side of housing 4372 and a motor 4376 and drive shaft (notshown). The drive shaft is disposed within housing 4372.

One of the pipette assemblies 4380 a-e is reserved for clean reagenttransfers, and, thus, a pipette tip 4062 carried by such reservedassembly 4380 is never contaminated by sample. This allows a singlereagent tip 4062 to be used for the entire extraction process,minimizing the number of tips required for an assay workflow. As eachpipette assembly 4380 a-e is capable of traveling independently in az-direction, pipette tip 4062 from such reserved pipettor 4380 can beindependently inserted through channels 4242 of piercing tool 4240 andinto the appropriate liquid-containing reservoir of plate 4050, as bestshown in FIG. 11 . There is no contact between pipette tip 4062 and asolid surface.

Each pipette assembly 4380 a-e is similar to the pipette assembly 502 ofFIGS. 17A-17D and pipette assembly 1402 of FIGS. 27A and 27B of the '349Application with the exception that each pipette assemblies 4380 a-e isnot hingedly connected to its respective main board assembly 4370 a-eand does not rotate into multiple hinge positions. Each pipette assembly4380 a-e is constrained from rotation and moves in a verticalz-direction along vertical rail 4374 via motor 4376. Thus, the first,second, third, fourth, and fifth pipette assemblies 4380 a-e are capableof moving independently in a vertical or z-direction. Otherwise pipetteassemblies 4380 a-e are constructed similarly to pipette assemblies 502and 1402 particularly with regard to its pipette channel assembly (notshown) and pipette tip ejector assembly.

Backplane connector 4360 is similar to the backplane connector 1600 ofFIGS. 29A and 29B of the '349 Application with the exception thatbackplane connector 4360 is configured to have multiple liquid handlingassemblies 4352 a-e and consumable handling assembly 4320 connectedthereto. In this regard, backplane connector 4360 connects to main boardassemblies 4370 a-e of each liquid handling assembly 4352 a-e and tocorresponding electronic boards that operate consumable handlingportion. Backplane connector 4360 includes several input and outputconnectors (not shown), such as Ethernet, multi-pin, positive pressureinput, and negative pressure input connectors for supplying theconsumable handling module 4320 and liquid handling assemblies 4352 a-ewith the requisite power, pressure, and data signals. This helps reduceor eliminate external cabling that could snag and can be difficult tomanage with multiple liquid handling assemblies 4352 a-e being connectedin such close proximity. The requisite inputs can be provided tobackplane connector 4360 via rotational stage 4310. In this regard,backplane connector 4360 may act as a manifold for air pressure andother inputs/outputs.

FIG. 15 depicts a general architecture of a computing system of analyzer4000. Computing system may be a subsystem within system 1300 of FIG. 26of the '349 Application which depicts a computing system diagram of thehigh-throughput system 00. In this regard, cross instrument bus 4404 andwork flow computing device 4540 are the same as bus 1320 and computingdevice 1330 depicted in FIG. 26 of the '349 Application. In addition,computing device 4410 is similar to computing device 1360 and isdescribed in more detail herein along with its inputs and outputs withinanalyzer 4000.

Computer Control Device & Processor

Computer control device 4400 may be any general purpose computer and maycontain a processor 4412, memory 4414 and other components typicallypresent in general purpose computer control devices. Although computercontrol device 4410 can include specialized hardware components toperform specific computing processes. Processor 4412 may be anyconventional processor, such as a commercially available CPU.Alternatively, processor 4412 may be a dedicated component such as anapplication specific integrated circuit (“ASIC”) or other hardware-basedprocessor.

Memory 4414 may store information accessible by processor 4412,including instructions 4416 that can be executed by processor 4412.Memory 4414 can also include data 4418 that can be retrieved,manipulated or stored by processor 4412. Memory 4414 can be of anynon-transitory type capable of storing information accessible byprocessor 4410, such as a hard-drive, memory card, ROM, RAM, DVD,CD-ROM, write-capable, and read-only memories.

Instructions 4416 can be any set of instructions to be executeddirectly, such as machine code, or indirectly, such as scripts, byprocessor 4412. In that regard, the terms “instructions,” “application,”“steps,” and “programs” can be used interchangeably herein. Instructions4416 can be stored in object code format for direct processing byprocessor 4412, or in any other computing device language includingscripts or collections of independent source code modules that areinterpreted on demand or compiled in advance.

In one embodiment of analyzer 4000, computing device 4410 may includeseveral sets of instructions 4416. For example, each assay to beperformed may have several sets of instructions associated with it whichmay include instructions that operate multipurpose robot 4300 tooptically scan consumables, grip and move consumables, and aspirateliquid samples.

Data 4418 can be entered and viewed through a graphical user interface(“GUI”) which may be displayed on display interface 4420 which isspecifically associated with analyzer 4000, or display interface 1332 ofFIG. 1 and FIG. 26 of the '349 Application which is associated with theentire high-throughput system 00. Data 4418 can also be entered fromvision system 4320 of multipurpose robot 4300 or scanners withinpre-analytical system 10. Data 4418 can also be obtained by sensors doorsensors, temperature sensors and the like, to obtain informationregarding certain conditions and activities occurring within analyzer,such as the location of particular consumables and air quality, forexample.

This data 4418 can be digitally tagged to particular identificationcodes (e.g., barcode serial numbers) in a field implemented orrelational database, which may also be stored in memory 4414. This helpsanalyzer 4000 keep track of various consumables within analyzer 4000 andhelps provide certain information to processor 4412 during the executionof processor instructions 4416 without the need for user input. Forexample, amplification plate 4050 may have an identification code whichmay be associated with a bar code located on an outer surface thereofwhich may be tagged in the database with certain stored data such as thetype of reagents stored therein and which reagents have already beenutilized. This allows analyzer to check its inventory to determine whenreagents and other consumables are running low or are insufficient toperform additional assays. In another example, a shuttle 4030 may havean identification code which may be tagged in the database with certainstored data such as data involving each of the sample containers 03carried by shuttle 4030 such as patient name, assay to be performed,processing parameters and the like. In a further example, when analysisis completed, the result of the assay can be associated with theparticular sample within the database so that a user can easily retrievethe results via access to the workflow computing device 4540 as suchresults may be communicated thereto by device 4410.

Although FIG. 15 functionally illustrates processor 4412, memory 4414,and other elements of computer control device 4410 as being within thesame block, computer control device 4410, processor 4412, and/or memory4414 can be comprised of multiple processors, computer control devices,and memories, respectively, which may or may not be stored within thesame physical housing. For example, memory 4414 can be a hard drive orother storage media located in housings different from that of computercontrol devices 4410. Accordingly, references to processor 4412,computer control device 4410, and memory 4414 should be understood toinclude references to a collection of processors, computer controldevices, and memories that may or may not operate in parallel.

Display Interface

Display interface 4420 may be associated specifically with analyzer 4000and may only display information regarding analyzer 4000 and may also beintegrated into the structure of analyzer 4000. However, displayinterface 4420 is optional (indicated by dashed lines in FIG. 15 ) and,in the embodiment depicted in FIG. 1 , is not included as the overallsystem display interface 1332 is utilized instead. However, wheredisplay interface 4420 is included, interface 4420 may be a monitor, LCDpanel, or the like coupled to a front panel of housing 4010 or locatedremote from analyzer 4000. Display interface can display a GUI, userprompts, user instructions and other information that may be relevant toa user.

Input Interface

User control/input interface 4430 allows a user to navigate the GUI, andagain, may be optionally provided as a separate component from theoverall system input interface which is provided by display interface1332 of FIG. 1 . However, where user control/input interface 4430 isprovided, such interface can be a touch panel, keyboard, or mouse, forexample. In addition, input interface 4430 can be integrated intodisplay interface 4420 such that the same device that displays promptsand the like is the same device that allows a user to respond to saidprompts.

As depicted in FIG. 15 , computer control device 4410 may be connectedto workflow computing device 4540 which is utilized to integrate all ofthe components of high-throughput system 00 such as the first analyzer2000 and pre-analytical system 10 and to integrate with a particularlylaboratory's laboratory information system (“LIS”) 4550. Thusinformation relevant to analyzer 4000 originating within pre-analyticalsystem 10 can be communicated to analyzer 4000 via workflow computingdevice 4540. Similarly, information relevant to pre-analytical system 10that originates in analyzer 4000 may be communicated via computercontrol device 4540 to workflow computing device 4540 which communicatesthat information to pre-analytical system 10. Such information can alsobe supplemented with information obtained from the LIS 4550 by workflowcomputing device 4540, such as patient information and the like.

Computer control device 4410 is also connected to multiple componentswithin analyzer 4000 to share information back and forth such asinstructions and data. Some of the components that are connected withcomputer control device via internal bus 4502 include several of thecomponents previously described that are on located on the processingdeck, such as the plate sealer and orbital shakers. In addition,computer control device may be connected to detector/readers 4260 a-band multipurpose robot 4300. Such connections with computer controldevice 4410 allows computer control device 4410 to provide instructionsto such components and receive information therefrom. For example,multipurpose robot 4300 may receive instructions from computer controldevice 4410 to retrieve and apply puncture tool 4240 to a reagent troughassembly 4050 or to pick up and move an amplification plate 4040 fromone location to another. Thus operations performed by the internalcomponents of analyzer 4000 are generally as a result of instructionsprovided by processor 4410 as analyzer 4000 is fully automated.

In a method 4600 of processing and analysis (FIG. 16 ) utilizinganalyzer 4000, analyzer 4000 moves samples through four functionalstages: sample transfer, extraction, pre-amplification, andamplification/detection. Such stages are now described.

Sample Transfer

Upon notification 4600 from pre-analytical system 10 that a batch ofsamples has been prepared (up to three shuttles 4030) and is ready fortransfer and analyzer 4000 acknowledges such notification, analyzer 4000advances to the sample transfer stage 4604. In the sample transferstage, pre-analytical system 10 feeds shuttles 4030 to analyzer 4000 viashuttle transport assembly 300 in a sequence of one to three shuttles4030. The size of the batches conveyed into the analyzer 4000 is amatter of design choice. For example, where three shuttles aretransferred, the first two shuttles 4030 may contain 12 samplecontainers 03 and the last shuttle 4030 may contain 8 sample containers.The first shuttle will typically include 2 control sample containersnumbering among the 12 sample containers carried thereby into theanalyzer. The two control sample containers will typically be in thefront of the shuttle as conveyed into the analyzer. Therefore, in thisexample, 30 sample containers are carried into analyzer in one batch,with two controls. These shuttles 4030 are handled one-at-a-time byanalyzer 4000 such that the samples contained in the shuttle 4030 arecompletely moved through the sample transfer process and returned topre-analytical system 10 before the next shuttle 4030 in the queue ismoved to analyzer 4000.

Shuttle Receipt and Clamping

As described in the '349 application, shuttle transport assembly 300 ofsystem 10 includes an input lane and an output lane wherein one of theseis dedicated for shuttle transfer to analyzer 4000 and one for shuttlereturn from analyzer 4000. Prior to receipt of shuttle 4030 frompre-analytical system 10, analyzer 4000 ensures conveyor 4254 of shuttleretention assembly 4250 is aligned with the appropriate lane of shuttletransport assembly 300. Thereafter, shuttle 4030 is fed out ofpre-analytical system 10, through a port between the side walls of thetwo systems 10, 4000, and onto conveyor 4254 within analyzer 4000. Thus,pre-analytical system 10 hands off a shuttle 4030 to analyzer 4000.

Once the shuttle 4030 has fully transitioned into analyzer 4000,pre-analytical system 10 ceases its feed mechanism and waits for a readyacknowledgement from analyzer 4000 to send a subsequent shuttle 4030.Meanwhile, analyzer 4000 moves shuttle 4030 to its dock position towardthe center of analyzer 4000 until it is positioned between clampingassembly 4252. Once the shuttle 4030 has been registered as being in itsdesired location through the use of optical sensors, clamping assembly4252 clamps about shuttle 4030 and engagement members 4253 engage skirts07 of sample containers 03, such as by piercing them, to hold them inplace for liquid transfer.

Thereafter, a pipette assembly 4380 penetrates a penetrable cap 09 ofone of sample containers 03 in shuttle 4030. The geometry of the piercedcap creates the possibility of a significant amount of lift force beinggenerated on container 03 by pipette assembly 4380 as the pipette tip4062 is removed from container 03 following aspiration. Engagementmembers 4253 help ensure that each container 03 remains seated.

Sample Aspiration and Transfer

Once shuttle 4030 with its containers 03 are fully seated and secured,analyzer 4000 moves to the sample aspiration and transfer portion of thesample transfer stage 4604. For each set of four containers 03 in theshuttle 4030, beginning with the pair of containers 03 in the innermostposition, pipettor 4350 uses two of its five pipette assemblies 4380with a pipette tip 4062 loaded thereon to pierce penetrable cap 09 ofeach pair of containers 03, mix the sample, and aspirate the requiredsample volume from the containers 03. Once the correct sample volume hasbeen aspirated, pipette tips 4062 are removed. A second pair of pipetteassemblies 4380 is used to perform the identical process on the nextpair of sample containers 03 in shuttle 4030 moving in a direction awayfrom the center of shuttle 4030.

Once four samples are aspirated and are disposed within pipette tips4062, multipurpose robot 4350 moves over to a pre-designated consumabledrawer 4120 and dispenses the four samples in one row of the 4×8 grid ofextraction containers 4026 which have been pre-punctured prior to thesample transfer process. Following dispensing of the samples intoextraction containers 4026, the four used pipette tips 4062 are ejectedthrough tip waste chute 4210. This process is repeated for the remainingtwo sets of four samples in shuttle 4030 (in the case of the thirdshuttle, the one remaining set of four), until the entire set ofcontainers 03 contained in the particular shuttle 4030 have beentransferred to extraction containers 4026.

Shuttle Return

Once samples from all containers 03 have been successfully transferredto extraction containers 4026, shuttle 4030 can be returned topre-analytical system 10. To prepare for this, clamping mechanism 4252on shuttle retention assembly 4250 is released, removing engagementmembers 4253 from containers 03 in shuttle 4030. Following negotiationof readiness between pre-analytical system 10 and analyzer 4000, shuttleretention assembly 4250 shifts itself in a forward-backward directionalong platform 4255 so that its conveyor 4254 aligns itself with asample return lane of shuttle transport assembly 300 in pre-analyticalsystem 10. Once retention assembly 4250 is in position, conveyor 4254 isused to pass shuttle 4030 out of analyzer 4000 and back topre-analytical system 10.

These steps are repeated until all three shuttles 4030 have beenreceived by analyzer 4000, had their samples transferred to anextraction container 4026, and returned to pre-analytical system 10. Atthat point, the sample transfer stage 4604 is completed. Thus, in thisembodiment, 32 tips have been consumed, and analyzer 4000 moves to theextraction stage 4606.

Extraction

Once all samples have been moved to the extraction containers 4026,analyzer 4000 begins extraction process 4606. During extraction, DNA iseluted from the samples and isolated to prepare for PCR amplification.Extraction stage 4606 is conducted using pipette assemblies 4380 a-e onmultifunctional robot 4300 and the extractors built into the particularconsumable drawer 4120 on which extraction is being performed.

Pipettor Usage

In order to minimize the number of tips 4062 required to perform theassay workflow, multifunctional robot 4300 includes five pipetteassemblies 4380 a-e. This allows analyzer 4000 to sequester a singlepipette assembly 4380 for clean reagent dispenses that do not makecontact with the sample and, thus, do not contaminate the tip withsample. This fifth pipettor 4380 finds its use in the extractionprotocol, reducing the frequency with which contaminated tips 4062 needto be disposed.

At some point prior to commencing extraction (either during a previousrun if sufficient bulk liquid reagent remained in the trough 4052 orwhen preparing for the run in question), a reagent trough assembly 4050is pierced with a puncture tool 4240, which is left in place to providechannel 4242 through which the reagent tip 4062 can aspirate liquidreagents. Puncture tool application is performed by gripper 4340 ofmultifunctional robot 4300, as is described in more detail above

Extractors

To help isolate the DNA that is extracted from the sample, it is boundto ferric oxide particles, which allows for their magnetic capture. Thisenables the DNA to be isolated from the rest of the unwanted sample,which can be washed away from the eluate using a wash buffer located intrough assembly 4050. In order to perform this isolation, a magneticfield is applied to extraction containers 4026. This is achieved throughthe use of an extractor module, which includes enough magnets to ensurethat each row of extraction containers 4026 is neighbored by a magnet onboth sides. Such magnets are selectively moved from a position belowextraction containers 4026 to a position adjacent such containers. Thisapplies the magnetic field which captures the bound DNA to a side ofextraction containers 4026.

Extraction Protocol

Extraction is achieved through the systematic addition of variousbuffers, engagement and disengagement of extractor magnets housed in theconsumable drawer and tip mixes. The full extraction operation generallyinvolves the use of 2 pipette tips 4062 per sample and uses, in thefollowing order, acid, wash, elution, and neutralization buffers.Analyzer 4000 processes sets of four samples at a time, allowed by thespacing of pipettors 4380. To start, the instrument extracts the DNA fora set of four samples using the acid, wash, and elution buffers andperforming sample mixes using a single set of tips, at which point theneutralization buffer is added and analyzer 4000 moves to the next setof four samples. Once DNA has been eluted from all samples, analyzer4000 uses a second set of four tips 4062 for each row of four samples toperform a neutralization mix (disposing of the tips after each mix), atwhich point the extracted DNA is ready for amplification and theinstrument moves to the pre-amplification stage 4608.

Pre-Amplification

The pre-amplification stage 4608 occurs once DNA extraction is finished,and is responsible for taking the extracted DNA left in extractioncontainers 4026, using it to rehydrate a master mix reagent in anamplification plate 4040, preparing amplification plate 4040 for PCR,and moving plate 4040 to the appropriate reader 4260. This process isachieved through use of multifunctional robot 4300 (both pipettors 4380and gripper 4340), the plate sealer 4220, and orbital mixer 4230.

Eluate Transfer

In order to move the eluted DNA from the extraction containers 4026 toamplification plate 4040, analyzer 4000 uses the sequestered/reservedpipette tip for each sample. Each of the 32 DNA samples is transferredinto three wells 4042 in amplification plate 4040. This is accomplishedthrough a triple dispense, wherein enough sample for all three dispensesis aspirated from four extraction containers 4026 at a time using foursample pipettors 4380. Following aspiration, robot 4300 moves overamplification plate 4040 and sequentially dispenses into each of thethree wells 4042 that are filled by each sample. Following thisdispense, three (predetermined) wells 4042 are filled with neutralizedDNA elution each. The used tips 4062 are then dropped into waste 4210,and the process is repeated for the remaining seven rows of fourextraction containers 4020.

Plate Sealing

Once the eluted DNA is transferred into amplification plate 4040, plate4040 is moved to plate sealer 4220 where it is sealed. To transportplate 4040, robot 4300 is positioned such that gripper mechanism 4340hovers over amplification plate 4040. Gripper arms 4344 a-b are opened,gripper 4340 is lowered, and arms 4344 a-b close to engage plate 4040.Sensors in the gripper arms 4344 a-b indicate when gripper teeth haveengaged plate 4040.

Once engaged, plate 4040 is lifted and transported by robot 4300 toplate sealer 4220. Plate 4040 is deposited in the waiting stage 4224 ofsealer 4220, arms 4344 a-b disengage, and gripper 4340 is clearedvertically. To apply the plate seal, sealer 4220 positions amplificationplate 4040 under a heated platen, feeds a section of cut seal materialover plate 4040, and lowers the platen to use heat and pressure to bondthe seal material to plate 4040. After sealing, the stage 4224 isejected and plate 4040 is available for transport.

Plate Mixing

Once plate 4040 has been sealed, rehydration of the master mix dry-downreagent within amplification plate 4040 is performed. Once again, plategripper module 4340 of robot 4300 engages and lifts plate 4040, andtransports it to a pre-selected orbital mixer 4230. Once plate 4040 hasbeen placed in mixer 4230, gripper arms engage to lock the plate inplace. To finalize rehydration, plate 4040 is spun at a speed thatensures full mixing of the eluate and dry-down reagent while avoidingsplashing of the liquid onto the plate seal.

Transfer to Reader

Once the plate 4040 has been fully processed for PCR amplification, itis transported into reader 4260 for amplification. To ready reader 4260to accept plate 4040, the reader cavity is opened and any plate 4040held in the reader is moved to waste 4004 using plate transfer module4320 on robot 4300. Robot 4300 then retrieves the released plate 4040from mixer 4230 and moves it to pre-selected reader 4260. Once plate4040 has been placed in reader 4260, amplification and detection canbegin.

Amplification and Detection

Once plate 4040 has been placed in reader 4260, analyzer controlsoftware, via processor 4412, initiates a PCR protocol which allowsreader 4260 to amplify the sample in place, monitor its real-timeamplification, and return curve data that can be translated into aresult on each of the molecular assay targets, in turn allowing fordetection and genotyping of HPV.

Assay Timing

The PCR protocol takes approximately 2 hours after initiation tocomplete. To maximize throughput, analyzer 4000 leverages the differencein the extraction (˜1 hr.) and amplification/detection (˜2 hr.)processes. Once a sample has been placed in reader 4260 and theamplification and detection stage 4610 has begun, a second set ofsamples can begin to move through the process. These samples will be fedinto the second reader 4260 b; starting PCR approximately 1 hour afterthe protocol in the first reader 4260 a starts. A third set of samplescan then be moved through the extraction process, finishing in time tobe placed in first reader 4260 a for PCR, which has recently finishedits first amplification. By alternating samples between the two readers4260 a-b, it is possible to maximize the number of samples moved throughthe extraction process.

A number of consumables are loaded on either a per-run or per-day basisby the user to ensure full assay throughput. In one embodiment,consumable drawers 4100 in analyzer 4000 provide a platform on whichsamples 03 are processed and DNA is extracted. Each of these is usedone-at-a-time, meaning that at any point, several are not in use (andeither in a loaded or consumed state). Analyzer 4000 is setup, viainstructions 4416 in its memory 4414, such that these drawers 4100 canbe ejected and accessed without requiring the user to access theinternal envelope of analyzer 4000 and halt the movement of robot 4300.At any point in time, a visual indicator (e.g., colored LED) on eachdrawer 4110, 4120 indicates its status (ready for use, in-use, spent).The user can access all drawers 4100 that are not currently in use atany point in time, so that all spent drawers can be replenished at theconvenience of the user.

When each drawer 4120 is ejected, the user removes and replaces the usedamplification container holders 4020 and empty tip holders 4060. Theuser also adds an unused amplification plate 4040 to drawer 4120. Oncedrawer 4120 is reinserted, the instrument re-inventories that particulardrawer 4120 to check for loading errors and to update its internalinventory, flagging the drawer as ready for an extraction.

Extraction Trough Reloading

Extraction trough assemblies 4050 contain sufficient liquid reagent forabout 18 extractions, which is enough to last for a full 24 hour periodat a maximum throughput. As it may be unknown how much throughput may beneeded for a particular day, two reagent trough assemblies 4050 sit onthe deck rather than one large trough assembly. This allows each troughto be fully consumed prior to using the second trough, minimizing waste.Since such troughs can last a 24 hour period, such troughs 4050 aretypically reloaded during a daily cleaning protocol. During operation,analyzer 4000 monitors volume and indicates to the user which, if any,troughs 4050 may need to be replaced.

One example of what is described herein is an automated analyzer having:i) a processing deck comprising a shuttle transfer station, the shuttletransfer station further comprising a conveyer for carrying a shuttlereceived by the automated analyzer to the shuttle transfer station, theshuttle being a rack comprising a plurality of receptacles, eachreceptacle adapted to receive a sample container; ii) a carrier for atleast one puncture tool disposed on the processing deck; iii) a robotcomprising a gripper; iv) a station configured to receive a consumablereagent trough. In this example, the robot, using the gripper, moves apuncture tool from the carrier to the station that receives a consumablereagent trough and lowers the puncture tool over the station configuredto receive a consumable reagent trough. In one example the robot is amultipurpose robot having: i) a gantry; and ii) a payload moveablyconnected to the gantry, the payload carrying the gripper and a pipettormodule having a plurality of pipette heads each being connectable to apipette tip. The gripper has a plurality of moveable arms capable ofcooperative lateral movement to grasp and release articles. The robotalso has a backplane connector having a housing and a plurality ofutility connectors coupled to the housing. The pipettor module andgripper are each connected to the housing of the backplane connector andthe plurality of utility connectors thereof in this example.

The above puncture tool carrier has a housing defining a cavitydimensioned to receive a puncture tool and a plurality of retainingmembers moveably connected to the housing. The plurality of retainingmembers are moveable from a first position in which the retainingmembers engage the puncture tool when present in the puncture toolcarrier to a second position in which the retaining members aredisengaged from the puncture tool allowing the puncture tool to beplaced in and removed from the carrier. In one example the puncture toolcarrier includes a plurality of posts extending from a base of thehousing. The posts may be tapered at the distal end of the post from thebase.

In one example, the gripper has at least two gripper arms. Each of theat least two gripper arms has a gripper finger attached thereto, wherethe gripper arms move laterally with respect to each other such that ina first position the gripper arms are spaced a lateral distance apartthat is greater than the lateral spaced apart distance in a secondposition. In a further example the gripper has at least two holdingmembers. For example, each of the at least two holding members moveslaterally with respect to each other such that in a first position theholding members are spaced a lateral distance apart that is greater thanthe lateral spaced apart distance in a second position.

In a further example, the at least two gripper fingers and/or the atleast two holding members each have a projection. In one example whenthe gripper is placed into the carrier, the gripper fingers engage andare biased against the retaining members when the gripper fingers are inthe first position and do not engage the retaining members when in thesecond position.

In one example, the puncture tool has a tool body and a plurality ofcannulated puncture members extending from the tool body, the cannulatedpuncture members each defining an opening extending through the toolbody and each being sized to allow a pipette tip to pass therethrough,each cannulated puncture member also defining an edge configured topenetrate a penetrable lid. The puncture tool comprises openings thatare configured to receive the posts when the puncture tool is placed inthe carrier.

In a further example the shuttle transfer station has a shuttleretaining platform that includes a jaw assembly with an open positionand a closed position, the jaw assembly being in the open position whenthe shuttle is received in the shuttle retaining platform. The jawassembly also has engagement projections. When the jaw assembly is inthe closed position, the engagement projections secure against lowerportions of containers carried by the shuttle. The jaw assembly isconfigured for the engagement projections to pass through openings inthe side of a shuttle received by the shuttle retaining platform whenthe jaw is in the closed position thereby urging the engagementprojections into contact with the lower portions of sample containersdisposed in the shuttle. The engagement projections do not extend intothe shuttle openings when the jaw is in the open position. In a furtherexample the jaw assembly has a drip shield that fastens around samplecontainers disposed in the shuttle when the jaws are in the closedposition. In a further example the shuttle retaining platform has aninput lane and an output lane and the shuttle retaining platformreceives the shuttle in the output lane and the shuttle retainingplatform is equipped with a driver that moves the jaw assembly with theshuttle therein from the output belt to the input belt.

Also described herein is an extraction container holder assembly with:i) a bottom tray comprising an array of openings; ii) a top tray havingan array of openings. When the bottom tray and the top tray areassembled together, the bottom openings align with the top openings. Theassembly includes an array of extraction tubes joined together as astrip. When the strip of extraction tubes is assembled with the bottomtray, the extraction tubes fit through the openings in the bottom trayand the strip prevents the tubes from passing through the openings sothat the strip rests on the top of the bottom tray. In one example thereis a layer disposed over the strip and the array of extraction tubessupported by the strip, and the layer formed over the extraction tubesis a seal and wherein the seal is a pierceable seal. In a furtherexample the bottom tray has upward facing sidewalls and, when the toptray is assembled with the bottom tray, the top tray fits within theconfines of the upward facing side walls of the bottom tray. The toptray of the assembly may have support ribs that are positioned on thetop try in a direction that is orthogonal to the strip supported by thebottom tray. The seals over the extraction tubes are exposed through theopenings in the top tray when the top and bottom trays are assembledtogether with the strip therebetween. In a further example a barcode isplaced on the top tray, wherein the information associated with the barcode includes at least one of a manufacturing lot of the extractiontubes, an expiration date of the extraction tubes or serial number ofthe extraction tubes. In a further example the bottom tray has a featureon the upwardly extending sidewalls thereon that engages with acorresponding feature in a drawer for housing the extraction containerassembly providing for an interference of the extraction tube containerassembly in the drawer.

Also described herein is a puncture tool assembly having: i) a puncturetool having a tool body and a plurality of cannulated puncture membersextending from the tool body, the cannulated puncture members eachdefining an opening extending through the tool body and each being sizedto allow a pipette tip to pass therethrough, each cannulated puncturemember also defining an edge configured to penetrate a penetrable lidand where each of the troughs is covered by the penetrable lid prior tobeing penetrated by respective cannulated puncture members; and ii) apuncture tool carrier having a housing defining a cavity dimensioned toreceive the puncture tool and a plurality of retaining members moveablyconnected to the housing, the plurality of retaining members beingmoveable from a first position in which the retaining members engage thepuncture tool to a second position in which the retaining members aredisengaged from the puncture tool. The puncture tool carrier may have aplurality of posts extending from a base of the housing. The posts maybe tapered at the distal end of the post from the base.

Also described herein is a multipurpose robot having: i) a gantry; andii) a payload moveably connected to the gantry. The payload has: i) apipettor module having a plurality of pipette heads each beingconnectable to a pipette tip; ii) a gripper module having a plurality ofmoveable arms for gripping consumable items; and iii) a backplaneconnector having a housing and a plurality of utility connectors coupledto the housing, the utility connectors being configured to supply atleast one of power, data or vacuum pressure to the payload and thepipettor module and gripper module are each connected to the housing ofthe backplane connector and the plurality of utility connectors thereof.In one example the gripper has at least two gripper arms, each of the atleast two gripper arm having gripper finger attached thereto. Thegripper arms move laterally with respect to each other such that in afirst position the gripper arms are spaced a lateral distance apart thatis greater than the lateral spaced apart distance in a second position.The gripper may have a plurality of holding members. In this example theat least two holding members move laterally with respect to each othersuch that in a first position the holding members are spaced a lateraldistance apart that is greater than the lateral spaced apart distance ina second position. In a further example the at least two gripper fingersand/or the at least two holding members each has a projection.

Also described is a method of obtaining reagents for an assay in anautomated analyzer, in which the following steps are performed: i)moving a robot payload to a puncture tool carrier in which is disposed apuncture tool, the robot payload carrying a pipettor module and agripper module, the gripper module having at least two gripper arms,each gripper arm comprising a holding member and a finger; ii) engagingprojections from the holding member of the gripper arm with acorresponding linking member of the puncture tool by moving the gripperarms from a first position to a second position; iii) moving the robotcarrying the puncture tool to a liquid container at a second location,the liquid container having one or more penetrable lids covering aplurality of compartments containing liquid reagents; iv) lowering thepuncture tool onto the liquid container so that cannulated puncturemembers extending from the puncture tool penetrate the one or more lidsof the liquid container and each cannulated puncture member enters adifferent compartment of the liquid container; v) releasing the puncturetool from the robot by translating the gripper arms inward and closertogether so that the projections withdraw from the linking member of thepuncture tool; vi) introducing a pipette tip of the pipettor modulethrough at least one of the cannulated puncture members and into contactwith the liquid reagent disposed in the compartment penetrated by thepuncture member; vii) aspirating a liquid reagent from the compartment;and viii)transferring the liquid reagent to a tube adapted to receive asample for analysis. In the method a respective pipette tip may beintroduced through each cannulated puncture member and into contact withliquid reagents in the compartment punctured by the respective puncturemember.

In another exemplary method for obtaining a sample for analysis, suchmethod includes the steps of: i) conveying a first shuttle carrying oneor more sample containers into a sample analyzer and into a shuttleretaining mechanism, the shuttle retaining mechanism having opposed armsdisposed along the sides of the shuttle conveyed therein; ii) moving theopposed arms from a first position in which the shuttle was received toa second position wherein, in the second position, engagement membersextending from each opposed arm engages a bottom portion of each samplecontainer disposed in the shuttle such that the engagement membersextend through openings in the shuttle when in the second position; iii)lowering a pipette tip through the sample cap of the container, therebypiercing a seal in the cap, the pipette tip extending into the sampledisposed in the sample container; iv) aspirating a sample from thesample container of the first shuttle with the pipettor; v) withdrawingthe pipette tip from the sample containers; the engagement membersremaining engaged with the bottom portion of each sample container asthe pipette is withdrawn; vi) moving the opposed arms from the secondposition back to the first position; and vii) conveying the firstshuttle away from the shuttle retaining mechanism in a second directionopposite the first direction. In such method the following additionalsteps may be performed: viii) moving the shuttle laterally from a firstlane through which the shuttle is advanced into the shuttle retainingmechanism to a second lane through which the shuttle is conveyed out ofthe analyzer.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

The invention claimed is:
 1. An extraction container holder assemblycomprising: a lower tray portion comprising an array of openings; anupper tray portion comprising an array of openings; wherein, when thelower tray portion and the upper tray portion are assembled together,the openings in the lower tray portion align with the openings in theupper tray portion; an array of extraction tubes joined together by astrip, each extraction tube having an open end and a closed end, whereinthe strip joins the open ends of each extraction tube, wherein, when thestrip of extraction tubes is assembled with the lower tray portion, theextraction tubes fit through the openings in the lower tray portion andthe strip prevents the extraction tubes from passing through theopenings in the lower tray portion so that the strip rests on and issupported by the lower tray portion, further comprising a continuouslayer disposed over the strip and the array of extraction tubes joinedtogether by the strip, the layer disposed below the upper tray portion,wherein the layer formed over the extraction tubes is a seal and whereinthe seal is a pierceable seal.
 2. The extraction container holderassembly of claim 1, wherein the lower tray portion further comprisesupward facing sidewalls and wherein, when the upper tray portion isassembled with the lower tray portion, the upper tray portion fitswithin the upward facing side walls of the lower tray portion.
 3. Theextraction container holder assembly of claim 1, wherein the upper trayportion has support ribs that are positioned on the upper tray portionin a direction that is orthogonal to the strip supported by the lowertray portion.
 4. The extraction container holder assembly of claim 1,wherein the seal over the extraction tubes is exposed through theopenings in the upper tray portion when the upper and lower trayportions are assembled together with the strip therebetween.
 5. Theextraction container holder assembly of claim 1, wherein a barcode isplaced on the upper tray portion, wherein information associated withthe bar code includes at least one of a manufacturing lot of theextraction tubes, an expiration date of the extraction tubes or a serialnumber of the extraction tubes.
 6. The extraction container holderassembly of claim 2, wherein the lower tray portion has a feature on theupward facing sidewalls thereon that engages with a correspondingfeature in a drawer for housing the extraction container holder assemblyproviding for an interference of the extraction container holderassembly in the drawer.
 7. The extraction container holder assembly ofclaim 1, wherein the strip is flush with the open ends of eachextraction tube.
 8. The extraction container holder assembly of claim 1,wherein the strip of extraction tubes is configured such that, when theextraction container holder assembly is assembled, the extraction tubeopenings are between the lower tray openings and the upper tray openingsand the extraction tubes do not extend into or through the openings inthe upper tray portion.